Despite the fact that nearly 90,000 men who are diagnosed each year with prostate cancer will ultimately develop recurrence (rising PSA despite negative imaging studies after attempted curative therapy) there is no clear standard of care for these patients. Developing effective treatment strategies in this population and challenging drug development niche would be significant because it could delay the onset of metastatic castration resistant prostate cancer (mCRPC), which is the stage of disease that is associated with morbidity and mortality. This proposal is designed to evaluate the immune responses induced by a therapeutic cancer vaccine in this group of patients with recurrent disease, correlate immune responses with clinical effect (changes in PSA kinetics and development of metastatic disease on imaging) and explore several experimental imaging platforms (endorectal MRI, F-18 DCFBC, Ferumoxytol enhanced MRI, Sodium Fluoride PET) to follow these patients. The findings on these scans will be compared to the findings on conventional imaging studies and changes will be correlated with the ability to mount immune responses to treatment. Patients will be treated with Prostvac and evaluated for PSA specific immune responses to the therapeutic cancer vaccine. This will be accomplished by evaluating T-cells for response to sequences of amino acids (15-mers) that span the full length of the PSA Protein. Additional immune responses to Prostvac will be evaluated in peripheral blood using flow-cytometry analysis of 30 markers allowing for the evaluation of 127 immune subsets. Clinically, we will prospectively determine if Prostvac slows PSA growth kinetics after 6 months of treatment as has been suggested by previous trials. In addition we will use experimental imaging platforms (Endorectal MRI, F-18 DCFBC, Ferumoxytol enhanced MRI, Sodium Fluoride PET) as methods to assess progression in patients with non-metastatic (by conventional bone scan and computed tomography) castration sensitive prostate cancer. If the therapeutic cancer vaccine Prostvac is found to slow the growth rate of prostate cancer, then it could lead to the development of a non-toxic therapy in this asymptomatic population which would have the potential of delaying the morbidity and mortality associated with mCRPC. Accompanying immune data from treated patients could also be further developed as biomarkers if they correspond to clinical outcomes. Correlating clinical responses and findings on conventional scans could also lead to the use of these new experimental imaging technologies in the development of other treatment strategies